chrX-141838356-G-C

Variant names:

• chrX-141838356-G-C
• rs373639857
• NM_138702.1:c.41G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138702.1(MAGEC3):​c.41G>C​(p.Ser14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,209,546 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: MAGEC3 NM_138702.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.565
• Publications: 0 publications found

Genes affected

MAGEC3 (HGNC:23798): (MAGE family member C3) This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07714102).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138702.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC3	NM_138702.1	MANE Select	c.41G>C	p.Ser14Thr	missense	Exon 1 of 8	NP_619647.1	Q8TD91-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC3	ENST00000298296.1	TSL:1 MANE Select	c.41G>C	p.Ser14Thr	missense	Exon 1 of 8	ENSP00000298296.1	Q8TD91-1

Frequencies

GnomAD3 genomes AF: 0.0000356 AC: 4 AN: 112387 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 182739 AF XY: 0.00

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1097159 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362597

African (AFR) AF: 0.000114 AC: 3 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54015

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841344

Other (OTH) AF: 0.0000217 AC: 1 AN: 46033

GnomAD4 genome AF: 0.0000356 AC: 4 AN: 112387 Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1 AN XY: 34541

African (AFR) AF: 0.000129 AC: 4 AN: 30895

American (AMR) AF: 0.00 AC: 0 AN: 10659

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6183

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53309

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.000214 Hom.: 1

Bravo AF: 0.000102

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0061	T
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.56
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.086
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.81	P
Vest4		0.14
MVP		0.014
MPC		0.028
ClinPred		0.041	T
GERP RS		0.43
PromoterAI		-0.0064	Neutral
Varity_R		0.22
gMVP		0.069
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373639857; hg19: chrX-140926142;